Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models

Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, we established stable populations of BPH-1, PNT1B and RWPE-1 immortalized human PrEC lines that constitutively express flag-tagged ERG3 (fERG). All fERG-expressing populations exhibited characteristics of in vitro and in vivo transformation. Microarray analysis revealed >2000 commonly dysregulated genes in the fERG-PrEC lines. Functional analysis revealed evidence that fERG cells underwent EMT and acquired invasive characteristics. The fERG-induced EMT transcript signature was exemplified by suppressed expression of E-cadherin and keratins 5, 8, 14 and 18; elevated expression of N-cadherin, N-cadherin 2 and vimentin, and of the EMT transcriptional regulators Snail, Zeb1 and Zeb2, and lymphoid enhancer-binding factor-1 (LEF-1). In BPH-1 and RWPE-1-fERG cells, fERG expression is correlated with increased expression of integrin-linked kinase (ILK) and its downstream effectors Snail and LEF-1. Interfering RNA suppression of ERG decreased expression of ILK, Snail and LEF-1, whereas small interfering RNA suppression of ILK did not alter fERG expression. Interfering RNA suppression of ERG or ILK impaired fERG-PrEC Matrigel invasion. Treating fERG-BPH-1 cells with the small molecule ILK inhibitor, QLT-0267, resulted in dose-dependent suppression of Snail and LEF-1 expression, Matrigel invasion and reversion of anchorage-independent growth. These results suggest that ILK is a therapeutically targetable mediator of ERG-induced EMT and transformation in PCa.

Secondary user relations in emerging mobile computing environments

Mobile technologies are enabling access to information in diverse environ.ments, and are exposing a wider group of individuals to said technology. Therefore, this paper proposes that a wider view of user relations than is usually considered in information systems research is required. Specifically, we examine the potential effects of emerging mobile technologies on end-­‐user relations with a focus on the ‘secondary user’, those who are not intended to interact directly with the technology but are intended consumers of the technology’s output. For illustration, we draw on a study of a U.K. regional Fire and Rescue Service and deconstruct mobile technology use at Fire Service incidents. Our findings provide insights, which suggest that, because of the nature of mobile technologies and their context of use, secondary user relations in such emerging mobile environments are important and need further exploration.

Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Making decisions about antibiotic use in the Australian primary healthcare sector

Introduction Australia is contributing to the global problem of antimicrobial resistance with one of the highest rates of antibiotic use amongst OECD countries. Data from the Australian primary healthcare sector suggests unnecessary antibiotics were prescribed for conditions that will resolve without it. If left unchecked, this will result in more resistant micro-organisms, against which antibiotics will be useless. There is a lack of understanding about what is influencing decisions to use antibiotics – what factors influences general practitioners (GPs) to prescribe antibiotics, consumers to seek antibiotics, and pharmacists to fill old antibiotic prescriptions? It is also not clear how these individuals trade-off between the possible benefits that antibiotics may provide in the immediate/short term, against the longer term societal risk of antimicrobial resistance. Method This project will investigate (a) what factors drive decisions to use antibiotics for GPs, pharmacists and consumers, and (b) how these individuals discount the future. Factors will be gleaned from published literature and from a qualitative phase using semi-structured interviews, to inform the development of Discrete Choice Experiments (DCEs). Three DCEs will be constructed – one for each group of interest – to allow investigation of which factors are more important in influencing (a) GPs to prescribe antibiotics, (b) consumers to seek antibiotics, and (c) pharmacists to fill legally valid but old or repeat prescriptions of antibiotics. Regression analysis will be conducted to understand the relative importance of these factors. A Time Trade Off exercise will be developed to investigate how these individuals discount the future, and whether GPs and pharmacists display the same extent of discounting the future, as consumers. Expected Results Findings from the DCEs will provide an insight into which factors are more important in driving decision making in antibiotic use for GPs, pharmacists and consumers. Findings from the Time Trade Off exercise will show what individuals are willing to trade for preserving the miracle of antibiotics. Conclusion The emergence of antibiotic resistance is inevitable. This research will expand on what is currently known about influencing desired behaviour change in antibiotic use, in the fight against antibiotic resistance. Real World Implications Research findings will contribute to existing national programs to bring about a reduction in inappropriate use of antibiotic in Australia. Specifically, influencing (1) how key messages and public health campaigns are crafted to increase health literacy, and (2) clinical education and empowerment of GPs and pharmacists to play a more responsive role as stewards of antibiotic use in the community.

Crime in rural Australia

As an academic who has spent a quarter of a century living, lecturing and researching in a rural community, I am often impressed by the discrepancies between the reality of rural life and its image in the public consciousness. At least two aspects of this are the most striking. First, there is often - especially, but not exclusively in English-speaking societies - the idea that rural communities represent the "real" or "true" aspects of a society's culture. For example, judging by the representations of rural Australia in the media, rural life is where we find the true Australian, the laconic, taciturn, but decent everyday man and woman, the "battlers", who are not corrupted by urban life. Such an attribution of genuineness to rurality is especially interesting given that the vast majority of contemporary Australians live in cities and that Australia is one of the most urbanised countries in the world. Second, and following from the first point, is the idea that rural areas remain somewhat behind the times, that somehow they are not quite part of the contemporary world. This is a mixed image as it combines both the negative idea of backwardness with the more positive one of a society that has not lost the virtues of stability and civility that we often feel is missing in the city. Both of these ideas combine in the popular image of rural communities as safe places in an increasingly dangerous world. In the popular mind it seems that there is an idea that whatever rural communities may lack in conveniences and sophistication, they remain places where you might walk down the street safely, leave your doors unlocked at night and raise your children confident that they will not be exposed to drugs, gangs and violence. Unfortunately, all of these ideas are fantasies. There is no reason to believe that the residents of rural communities are anymore the truer representations of Australian culture than the average suburbanite.

Young People and Crime in Rural Communities

Because childhood and adolescence are crucial phases in psycho-social development and the formation of responsible citizens, an unusual degree of attention and supervision is directed at the young (Bittner, 1976; Rose, 1989). Such is the moral frailty of youth that mere presence or 11 doing nothing" (Corrigan, 1979) can, under certain circumstances, excite adult anxieties as a harbinger of immediate or later danger. Delinquency and adolescent antisocial behaviour are not, therefore, a matter of objective, positivistic measurement and control, but are bound up with larger patterns of intergenerational relationships. These relationships are also conditioned by social and spatial environments.

Policing in Rural Australia: The country cop as law enforcer and local resident

The strategies and techniques that police officers employ are adaptations to the types of communities they serve and the law enforcement system of which they are part. Observations of policing in rural and urban areas of Australia indicate that, despite being part of a single state police service, officers develop working philosophies that are systematically adapted to the locations they serve. Bayley (1989) has observed that while crimes are policed in the city, people are policed in the country. Rural police officers often adopt a community-based model of policing in which officers become integrated into a community and establish compatible community relations. While this model can produce successful results, with integration into informal social networks providing police increased opportunities to solve crime, rural police regularly find themselves occupying competing roles of law enforcer and local resident. This chapter will outline how the organisation and structure of rural communities impacts upon policing, noting distinct issues associated with police work in rural settings. Before examining current aspects of rural policing, a brief discussion of the historical and cultural context of rural policing is provided.

Introduction - There's crime out there, but not as we know it: Rural criminology - the last frontier

The idea that crime is a predominantly urban phenomenon has been pervasive in criminology, so much so that Australian criminology textbooks do not recognise rural crime as a distinct phenomenon worthy of scholarly attention (see Chappell & Wilson, 2000; Goldsmith et al, 2003; White & Haines, 2004; White & Habibis, 2005). There are no chapters or sections in Australian texts which specifically examine rural crime, despite the inclusion of a range of topics that appear to provide a broad coverage of crime in its many temporal and spatial dimensions. Nor is there so much as an index reference to "rural" issues in criminology textbooks. The standardised syllabus for crime texts provides coverage of topics such as violent crime, public crime, delinquency, race and crime, gender and crime, and crime and social class. This canon is mirrored in international texts, most of which also fail to address the issue of rural crime, but make abundant reference to crime in various urban contexts (see Carrabine et al, 2004; Conklin, 2004). This is not to suggest that Australian texts fail to localise their subject matter.

Evaluation of Indigenous justice programs.: final report / Project D, Safe Aboriginal Youth Patrol Programs in New South Wales and Northbridge Policy and Juvenile Aid Group in Western Australia

The Australian Government has provided funding to evaluate the effectiveness of Indigenous law and justice programs across five subject areas to identify the best approaches to tackling crime and justice issues and better inform government funding decisions in the future. This report presents the findings of subject area "D", which examined two different approaches to delivering community and night patrol services for young people: the Safe Aboriginal Youth Patrol programs in New South Wales, and the Northbridge Policy project (the Young People in Northbridge project), in Western Australia. Night patrols can address crime either directly or indirectly, by prevention work or by addressing the social causes of crime through community development.

Development of an education program to improve care of patients with dementia in an acute care setting

As the population ages, the number of people with dementia in acute care environments is projected to increase rapidly. However, many acute care nurses have undertaken little or no dementia training, potentially leading to reduced quality of care for these patients. This article details the development and delivery of a tailored education program to improve the quality of care of people with dementia in a large, urban hospital in Australia. Designed specifically for the existing context, environment and knowledge levels, the program was developed from multiple inputs, including: expert opinion, literature on workplace and dementia care training, and feedback from participants. The program was delivered to acute care nurses and allied health staff within an outcome based, microteaching model. The broader applicability of the development and delivery techniques used in this program is also discussed.

Who really pays for urban infrastructure? : the impact of developer infrastructure charges on housing affordability in Brisbane, Australia

This thesis advances the understanding of the impact of developer infrastructure charges on housing affordability in Brisbane, Australia through the development of an econometric model and empirical analysis. The results indicate substantial on-passing of these government charges to purchasers of both new and existing homes, thus negatively impacting housing affordability across the whole community. The results of this thesis will inform policy makers and assist in the development of evidence based policy related to housing affordability and funding of urban infrastructure. Being generic, the econometric model is expected to be a tool that is suitable for estimating similar house price effects in other housing markets.

Multiple perspectives on quality of life for residents with dementia in long term care facilities: Protocol for a comprehensive Australian study

Background Dementia is a chronic illness without cure or effective treatment, which results in declining mental and physical function and assistance from others to manage activities of daily living. Many people with dementia live in long term care facilities, yet research into their quality of life (QoL) was rare until the last decade. Previous studies failed to incorporate important variables related to the facility and care provision or to look closely at the daily lives of residents. This paper presents a protocol for a comprehensive, multi-perspective assessment of QoL of residents with dementia living in long term care in Australia. A secondary aim is investigating the effectiveness of self-report instruments for measuring QoL. Methods The study utilizes a descriptive, mixed methods design to examine how facility, care staff, and resident factors impact QoL. Over 500 residents with dementia from a stratified, random sample of 53 facilities are being recruited. A sub-sample of 12 residents is also taking part in qualitative interviews and observations. Conclusions This national study will provide a broad understanding of factors underlying QoL for residents with dementia in long term care. The present study uses a similar methodology to the US-based Collaborative Studies of Long Term Care (CS-LTC) Dementia Care Study, applying it to the Australian setting.